Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study

TY - JOUR

T1 - Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis

T2 - The MIRROR study

AU - Bar-Or, Amit

AU - Grove, Richard A

AU - Austin, Daren J

AU - Tolson, Jerry M

AU - VanMeter, Susan A

AU - Lewis, Eric W

AU - Derosier, Frederick J

AU - Lopez, Monica C

AU - Kavanagh, Sarah T

AU - Miller, Aaron E

AU - Sorensen, Per S

N1 - © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2018

Y1 - 2018

N2 - Objective To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS).MethodsPatients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured. Safety monitoring continued weeks 24 to 48 with subsequent individualized follow-up evaluating B-cell repletion.ResultsThe cumulative number of new lesions was reduced by 65% for all ofatumumab dose groups vs placebo (p < 0.001). Post hoc analysis (excluding weeks 1-4) estimated a ≥90% lesion reduction vs placebo (week 12) for all cumulative ofatumumab doses ≥30 mg/12 wk. Dose-dependent CD19 B-cell depletion was observed. Notably, complete depletion was not necessary for a robust treatment effect. The most common adverse event was injection-related reactions (52% ofatumumab, 15% placebo), mild to moderate severity in 97%, most commonly associated with the first dose and diminishing on subsequent dosing.ConclusionImaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses ≥30 mg/12 wk), with a safety profile consistent with existing ofatumumab data. This treatment effect also occurred with dosage regimens that only partially depleted circulating B cells.Classification of evidenceThis study provides Class I evidence that for patients with RMS, ofatumumab decreases the number of new MRI gadolinium-enhancing lesions 12 weeks after treatment initiation.

AB - Objective To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS).MethodsPatients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured. Safety monitoring continued weeks 24 to 48 with subsequent individualized follow-up evaluating B-cell repletion.ResultsThe cumulative number of new lesions was reduced by 65% for all ofatumumab dose groups vs placebo (p < 0.001). Post hoc analysis (excluding weeks 1-4) estimated a ≥90% lesion reduction vs placebo (week 12) for all cumulative ofatumumab doses ≥30 mg/12 wk. Dose-dependent CD19 B-cell depletion was observed. Notably, complete depletion was not necessary for a robust treatment effect. The most common adverse event was injection-related reactions (52% ofatumumab, 15% placebo), mild to moderate severity in 97%, most commonly associated with the first dose and diminishing on subsequent dosing.ConclusionImaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses ≥30 mg/12 wk), with a safety profile consistent with existing ofatumumab data. This treatment effect also occurred with dosage regimens that only partially depleted circulating B cells.Classification of evidenceThis study provides Class I evidence that for patients with RMS, ofatumumab decreases the number of new MRI gadolinium-enhancing lesions 12 weeks after treatment initiation.

U2 - 10.1212/WNL.0000000000005516

DO - 10.1212/WNL.0000000000005516

M3 - Journal article

C2 - 29695594

SN - 0028-3878

VL - 90

SP - e1805-e1814

JO - Neurology

JF - Neurology

IS - 20

ER -